Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men

Aims: Improving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men. Met...

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Main Authors: Jordi P.D. Kleinloog, Ronald P. Mensink, Ellen T.H.C. Smeets, Dimo Ivanov, Peter J. Joris
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:NeuroImage: Clinical
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2213158222001802
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author Jordi P.D. Kleinloog
Ronald P. Mensink
Ellen T.H.C. Smeets
Dimo Ivanov
Peter J. Joris
author_facet Jordi P.D. Kleinloog
Ronald P. Mensink
Ellen T.H.C. Smeets
Dimo Ivanov
Peter J. Joris
author_sort Jordi P.D. Kleinloog
collection DOAJ
description Aims: Improving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men. Methods: Eighteen apparently healthy men, aged 18–60 years and with a waist circumference ≥ 102 cm, participated in a randomized, double-blind, placebo-controlled cross-over trial. The study consisted of two test days separated by at least one week. Men received in random order a drink providing 10 mmol (i.e., 625 mg nitrate) potassium nitrate or an isomolar placebo drink with potassium chloride. Brain insulin action was assessed 120–150 min after the drinks by quantifying acute effects of nasal insulin on regional CBF using arterial spin labeling Magnetic Resonance Imaging. Glucose and insulin concentrations were measured at regular intervals, while blood pressure was determined fasted and at 240 min. Results: Inorganic nitrate intake increased regional insulin action in five brain clusters. The two largest clusters were located in the right temporal lobe (ΔCBF: 7.0 ± 3.8 mL/100 g/min, volume: 5296 mm3, P < 0.001; and ΔCBF: 6.5 ± 4.3 mL/100 g/min, volume: 3592 mm3, P < 0.001), while two other cortical clusters were part of the right frontal (ΔCBF: 9.0 ± 6.0 mL/100 g/min, volume: 1096 mm3, P = 0.007) and the left parietal lobe (ΔCBF: 6.1 ± 4.3 mL/100 g/min, volume: 1024 mm3, P = 0.012). One subcortical cluster was located in the striatum (ΔCBF: 5.9 ± 3.2 mL/100 g/min, volume: 1792 mm3, P < 0.001). No effects of nitrate were observed on CBF before administration. Following nitrate intake, circulating nitrate plus nitrite concentrations increased over time (P = 0.003), but insulin and glucose concentrations and blood pressure did not change. Conclusion: Acute inorganic nitrate intake may improve regional brain insulin action in abdominally obese men. These regions are involved in the regulation of different metabolic and cognitive processes.The trial was registered on January 6th, 2021 at ClinicalTrials.gov as NCT04700241.
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spelling doaj.art-dd113390fa644740a3bb07c58eef97d42022-12-22T01:24:55ZengElsevierNeuroImage: Clinical2213-15822022-01-0135103115Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese menJordi P.D. Kleinloog0Ronald P. Mensink1Ellen T.H.C. Smeets2Dimo Ivanov3Peter J. Joris4Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The NetherlandsDepartment of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The NetherlandsDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Corresponding author at: Department of Nutrition and Movement Sciences, Maastricht University, PO Box 616, Maastricht 6200 MD, The Netherlands.Aims: Improving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men. Methods: Eighteen apparently healthy men, aged 18–60 years and with a waist circumference ≥ 102 cm, participated in a randomized, double-blind, placebo-controlled cross-over trial. The study consisted of two test days separated by at least one week. Men received in random order a drink providing 10 mmol (i.e., 625 mg nitrate) potassium nitrate or an isomolar placebo drink with potassium chloride. Brain insulin action was assessed 120–150 min after the drinks by quantifying acute effects of nasal insulin on regional CBF using arterial spin labeling Magnetic Resonance Imaging. Glucose and insulin concentrations were measured at regular intervals, while blood pressure was determined fasted and at 240 min. Results: Inorganic nitrate intake increased regional insulin action in five brain clusters. The two largest clusters were located in the right temporal lobe (ΔCBF: 7.0 ± 3.8 mL/100 g/min, volume: 5296 mm3, P < 0.001; and ΔCBF: 6.5 ± 4.3 mL/100 g/min, volume: 3592 mm3, P < 0.001), while two other cortical clusters were part of the right frontal (ΔCBF: 9.0 ± 6.0 mL/100 g/min, volume: 1096 mm3, P = 0.007) and the left parietal lobe (ΔCBF: 6.1 ± 4.3 mL/100 g/min, volume: 1024 mm3, P = 0.012). One subcortical cluster was located in the striatum (ΔCBF: 5.9 ± 3.2 mL/100 g/min, volume: 1792 mm3, P < 0.001). No effects of nitrate were observed on CBF before administration. Following nitrate intake, circulating nitrate plus nitrite concentrations increased over time (P = 0.003), but insulin and glucose concentrations and blood pressure did not change. Conclusion: Acute inorganic nitrate intake may improve regional brain insulin action in abdominally obese men. These regions are involved in the regulation of different metabolic and cognitive processes.The trial was registered on January 6th, 2021 at ClinicalTrials.gov as NCT04700241.http://www.sciencedirect.com/science/article/pii/S2213158222001802Abdominally obeseArterial spin labellingBrain insulin actionCerebral blood flowIntranasal insulin sprayInorganic nitrate
spellingShingle Jordi P.D. Kleinloog
Ronald P. Mensink
Ellen T.H.C. Smeets
Dimo Ivanov
Peter J. Joris
Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
NeuroImage: Clinical
Abdominally obese
Arterial spin labelling
Brain insulin action
Cerebral blood flow
Intranasal insulin spray
Inorganic nitrate
title Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
title_full Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
title_fullStr Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
title_full_unstemmed Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
title_short Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men
title_sort acute inorganic nitrate intake increases regional insulin action in the brain results of a double blind randomized controlled cross over trial with abdominally obese men
topic Abdominally obese
Arterial spin labelling
Brain insulin action
Cerebral blood flow
Intranasal insulin spray
Inorganic nitrate
url http://www.sciencedirect.com/science/article/pii/S2213158222001802
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